PROJECT SUMMARY This application is in response to the Priorities for Strategy 2.2 of the NIMH strategic plan, which calls for developing novel behavioral assessment tools that can be used across ages, sexes, species, and cultures to evaluate dysfunction in domains relevant to mental illnesses. We propose that mobile cognitive testing represents a promising complementary tool to traditional neuropsychological assessment methods with the potential to change the way research is conducted for individuals with bipolar disorder, and ultimately other patients with serious mental illness. Cognition is an important phenotype for a variety of genomic studies and large-scale population observational and intervention studies, yet to conduct traditional neuropsychological assessments in these studies is often infeasible due to the need for a skilled professional and high costs associated with in-person assessment. In addition, subtle or early cognitive deficits, such as those often observed in bipolar disorder, are difficult to detect with single administration neuropsychological tests. Our pilot work indicates that mobile cognitive tests may be more sensitive to these subtle deficits and reduce sources of bias and error associated with single administration tests. This suggests that mobile cognitive tests could have significant implications for large-scale population genomic studies, community-based intervention studies to obtain cognitive phenotypes, and/or clinical trials. We will refine and validate a battery of repeatable mobile cognitive tests of frontal systems (inhibition, working memory, processing speed), designed to facilitate the self-administration of cognitive assessments from smartphones, in a sample of community-dwelling, treated outpatients with bipolar disorder (Specific Aim 1), test the overarching hypotheses that within individuals, mood symptoms dynamically influence real-time cognition (Specific Aim 2), and that real-time cognition relates to real-time daily functioning (Specific Aim 3). Our study design will allow for the assessment of cognition at both inter- and intra-individual levels by utilizing a neurocognitive Ecological Momentary Assessment (EMA) protocol to obtain longitudinal data on cognition, mood, and daily functioning. The findings of this project will yield an understanding of within-person and between-person variability in cognition and mood in bipolar disorder. Results will also have implications for studying individuals from other clinical populations who have frontal system impairments, and will provide a foundation for improvements in cognitive testing in large-scale studies.